Structure–antibacterial activity of arylcarbonyl- and arylsulfonyl-piperazine 5-triazolylmethyl oxazolidinones

• Published in: European journal of medicinal chemistry 2007-02, Vol.42 (2), p.214-225
• Main Authors: Phillips, Oludotun A., Udo, Edet E., Ali, Ahmed A.M., Samuel, Santhosh M.
• Format: Article
• Language: English
• Subjects: 5-Triazolylmethyl-oxazolidinone; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Arylcarbonyl; Arylsulfonyl; Biological and medical sciences; Colony Count, Microbial; Drug Resistance, Bacterial; Gram-Negative Bacteria - drug effects; Gram-Negative Bacteria - isolation & purification; Gram-Positive Bacteria - drug effects; Gram-Positive Bacteria - isolation & purification; Linezolid; Medical sciences; Microbial Sensitivity Tests; Oxazolidinones - chemical synthesis; Oxazolidinones - chemistry; Oxazolidinones - pharmacology; PH-027; Pharmacology. Drug treatments; Piperazines - chemical synthesis; Piperazines - chemistry; Piperazines - pharmacology; Stereoisomerism; Structure-Activity Relationship; Sulfones - chemical synthesis; Sulfones - chemistry; Sulfones - pharmacology; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2006.10.005

A series of novel arylcarbonyl- and arylsulfonyl-piperazinyl 5-triazolylmethyl oxazolidinones were synthesized and tested against a panel of Gram-positive and Gram-negative bacterial clinical isolates. The arylcarbonyl oxazolidinone derivatives showed strong in vitro antibacterial activity against susceptible and resistant Gram-positive pathogenic bacteria and were more active than the arylsufonyl derivatives. Substitution of varied electron-withdrawing and electron-donating groups on the phenyl ring in the arylcarbonyl series did not alter antibacterial activity significantly. However, in the arylsufonyl series, methyl substitution on the phenyl ring resulted in the loss of antibacterial activity. Antibacterial activity could not be directly correlated with the calculated partition coefficient (Clog P) values in this series of compounds. [Display omitted] Synthesis and structure–antibacterial activity relationships of new 5-triazolylmethyl oxazolidinones are presented.